Validation of Hemoglobin A1c in Patients With Inflammatory Arthritis Treated With Sulfasalazine

Overview

The purpose of this study is to examine whether the blood test Hemoglobin A1c (HbA1c) gives an accurate picture of blood glucose levels in patients with inflammatory arthritis who are treated with sulfasalazine. HbA1c is widely used to diagnose and monitor diabetes, but sulfasalazine can shorten red blood cell lifespan and thereby lower HbA1c values independently of actual glucose levels. This may lead to underdiagnosis of diabetes in patients who develop diabetes during sulfasalazine treatment, and to undertreatment in patients with known diabetes due to falsely reassuring HbA1c values. The study aims to answer two main questions: 1. How many patients treated with sulfasalazine have undiagnosed diabetes despite having HbA1c values below the diagnostic threshold? 2. Does HbA1c underestimate actual glucose levels when compared with continuous glucose monitoring (CGM) in patients with sulfasalazine-treated inflammatory arthritis, both in those with known diabetes and those that are not diagnosed with diabetes but have borderline HbA1c values (≥ 38 mmol/mol)?

HbA1c is widely used to diagnose diabetes and to monitor long-term glycaemic control. HbA1c reflects average blood glucose levels over approximately two months but can be influenced by factors unrelated to glucose, including changes in red blood cell lifespan. Sulfasalazine, a disease-modifying antirheumatic drug commonly used to treat inflammatory arthritis, is known to cause mild haemolysis in some patients, which can lower HbA1c values independently of actual glucose levels. This effect may have important clinical consequences. In patients without diabetes at the start of sulfasalazine treatment, HbA1c values may remain below diagnostic thresholds even if diabetes develops over time, potentially delaying diagnosis. In patients with established diabetes, sulfasalazine-associated lowering of HbA1c may give a misleading impression of adequate glycaemic control, which may result in insufficient treatment intensification despite elevated true glucose levels. Together, these mechanisms may contribute to underdiagnosis and undertreatment of diabetes in patients receiving sulfasalazine. CGM provides direct, sensor-based measurements of interstitial glucose levels and is not affected by red blood cell turnover. CGM therefore offers an opportunity to assess actual glycaemic exposure independently of HbA1c. However, prospective data comparing HbA1c with CGM-derived glucose measures in sulfasalazine-treated patients with inflammatory arthritis are lacking. This study is a prospective observational investigation conducted in patients with inflammatory arthritis treated with sulfasalazine. Participants include both individuals with known diabetes and individuals without known diabetes who have HbA1c values in the borderline range. Each participant undergoes a single study phase in which blinded CGM is worn for up to 14 days, with blood sampling performed within the same time period. In participants without known diabetes, fasting plasma glucose measurements are used to evaluate the presence of previously unrecognised diabetes. By comparing HbA1c values with CGM-derived average glucose levels, the study aims to evaluate whether HbA1c accurately reflects glycaemic status in sulfasalazine-treated patients. The results are expected to improve understanding of the limitations of HbA1c in this clinical context and to inform future strategies for diabetes diagnosis and monitoring in patients receiving sulfasalazine, including the potential need for alternative or supplementary glucose assessment methods.